GRK5

G protein-coupled receptor kinase 5, the group of AGC family kinases|MicroRNA protein coding host genes

Basic information

Region (hg38): 10:119207570-119459745

Previous symbols: [ "GPRK5" ]

Links

ENSG00000198873 ∙ NCBI:2869 ∙ OMIM:600870 ∙ HGNC:4544 ∙ Uniprot:P34947 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GRK5 gene.

• Inborn genetic diseases (20 variants)
• not provided (10 variants)
• Neurodevelopmental disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GRK5 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	1	2
missense			22		4	26
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1	2	3
Total	0	0	22	2	7

Variants in GRK5

This is a list of pathogenic ClinVar variants found in the GRK5 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-119207947-GG-CT		Neurodevelopmental disorder	Uncertain significance (Jan 01, 2019)
10-119250744-A-G			Benign (Feb 24, 2021)
10-119326564-T-G		not specified	Uncertain significance (Feb 05, 2024)
10-119326578-A-G		not specified	Uncertain significance (Apr 25, 2023)
10-119326594-A-G		not specified	Uncertain significance (Mar 07, 2024)
10-119326608-A-T		not specified	Uncertain significance (Dec 05, 2022)
10-119380821-A-T		not specified	Uncertain significance (Jun 29, 2023)
10-119380822-T-G		not specified	Uncertain significance (Dec 07, 2021)
10-119396761-C-T		not specified	Uncertain significance (Oct 02, 2023)
10-119423182-C-T			Benign (Jun 29, 2018)
10-119423247-C-A			Benign (Jul 23, 2018)
10-119423275-C-T			Benign (Jun 29, 2018)
10-119423276-G-A			Likely benign (Apr 03, 2018)
10-119425003-G-A		not specified	Uncertain significance (Mar 20, 2023)
10-119425003-G-C		not specified	Uncertain significance (Jun 24, 2022)
10-119430387-C-G		GRK5-related disorder	Likely benign (Oct 07, 2021)
10-119430399-C-A		not specified	Uncertain significance (Jun 10, 2022)
10-119431391-G-A		not specified	Uncertain significance (Jan 26, 2022)
10-119431435-C-T		not specified	Uncertain significance (Jun 18, 2021)
10-119436768-G-A		not specified	Uncertain significance (Aug 28, 2023)
10-119436792-G-C		not specified	Uncertain significance (Nov 17, 2023)
10-119436834-G-A		not specified	Uncertain significance (Dec 18, 2023)
10-119442047-G-A		not specified	Uncertain significance (Sep 29, 2022)
10-119442058-C-T		not specified	Uncertain significance (Jun 23, 2023)
10-119442061-G-A		not specified	Uncertain significance (Feb 28, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GRK5	protein_coding	protein_coding	ENST00000392870	16	248031

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.676	0.324	125729	0	19	125748	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.16	245	360	0.680	0.0000218	3904
Missense in Polyphen		99	161.89	0.61154		1686
Synonymous	0.377	144	150	0.961	0.0000101	1075
Loss of Function	4.33	7	34.4	0.204	0.00000171	405

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000260	0.000260
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000475	0.0000462
European (Non-Finnish)	0.0000799	0.0000791
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine/threonine kinase that phosphorylates preferentially the activated forms of a variety of G-protein- coupled receptors (GPCRs). Such receptor phosphorylation initiates beta-arrestin-mediated receptor desensitization, internalization, and signaling events leading to their down-regulation. Phosphorylates a variety of GPCRs, including adrenergic receptors, muscarinic acetylcholine receptors (more specifically Gi-coupled M2/M4 subtypes), dopamine receptors and opioid receptors. In addition to GPCRs, also phosphorylates various substrates: Hsc70- interacting protein/ST13, TP53/p53, HDAC5, and arrestin-1/ARRB1. Phosphorylation of ARRB1 by GRK5 inhibits G-protein independent MAPK1/MAPK3 signaling downstream of 5HT4-receptors. Phosphorylation of HDAC5, a repressor of myocyte enhancer factor 2 (MEF2) leading to nuclear export of HDAC5 and allowing MEF2- mediated transcription. Phosphorylation of TP53/p53, a crucial tumor suppressor, inhibits TP53/p53-mediated apoptosis. Phosphorylation of ST13 regulates internalization of the chemokine receptor. Phosphorylates rhodopsin (RHO) (in vitro) and a non G- protein-coupled receptor, LRP6 during Wnt signaling (in vitro). {ECO:0000269|PubMed:19661922, ECO:0000269|PubMed:19801552, ECO:0000269|PubMed:20038610, ECO:0000269|PubMed:20124405, ECO:0000269|PubMed:21728385}.
• Pathway: Endocytosis - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);Morphine addiction - Homo sapiens (human);Myometrial Relaxation and Contraction Pathways;Chemokine signaling pathway;Calcium Regulation in the Cardiac Cell;Signaling by GPCR;Signal Transduction;G alpha (s) signalling events;IL-7 signaling;JAK STAT pathway and regulation;EPO signaling;VEGF;G alpha (q) signalling events;GPCR downstream signalling;Alpha-synuclein signaling (Consensus)

Recessive Scores

• pRec: 0.172

Intolerance Scores

• loftool: 0.241
• rvis_EVS: 0.05
• rvis_percentile_EVS: 57.48

Haploinsufficiency Scores

• pHI: 0.309
• hipred: Y
• hipred_score: 0.765
• ghis: 0.541

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.985

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Grk5
• Phenotype: endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); muscle phenotype; homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; normal phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype

Zebrafish Information Network

• Gene name: grk5l
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: curled

Gene ontology

• Biological process: apoptotic process;G protein-coupled receptor signaling pathway;adenylate cyclase-modulating G protein-coupled receptor signaling pathway;tachykinin receptor signaling pathway;regulation of G protein-coupled receptor signaling pathway;positive regulation of cell population proliferation;Wnt signaling pathway;negative regulation of apoptotic process;fat cell differentiation;protein autophosphorylation;regulation of cell cycle
• Cellular component: cytoplasm;cytosol;plasma membrane;nuclear speck;nuclear membrane
• Molecular function: protein serine/threonine kinase activity;G protein-coupled receptor kinase activity;protein kinase C binding;protein binding;ATP binding;phospholipid binding;beta-adrenergic receptor kinase activity